Osteoarthritis (OA) is a joint disorder, which is presumably induced by degeneration in articular cartilage as a main cause and frequently observed in e.g., the knee, hip and femur joints. OA is caused by not only aging and overload but also sports injury and obesity. Particularly, the number of patients with knee osteoarthritis is estimated to be 25,300,000 in Japan (ROAD project, the 22nd Century Medical and Research Center, The University of Tokyo Hospital, 2009) and is twice or more larger in the United States than in Japan. Also, in densely populated areas such as China, India and African countries where e.g., working conditions and environmental conditions are considered to be severer than in Japan, the number of OA patients will increase from now on. At present, in Japan, 75,000 (Yano Research Institute Ltd., 2011) patients are reported to undergo total artificial knee joint replacement surgery as a final therapy. Artificial joint replacement per se is a highly invasive therapy. In addition, the mechanical life of the artificial joint is limited and depending on circumstances, the artificial joint must be repeatedly exchanged.
In order to prevent exacerbation of knee osteoarthritis and avoid ultimate artificial joint replacement surgery, it is important to receive an appropriate treatment early. For early treatment, early detection of cartilage degeneration is required; however, it is difficult to detect early-stage cartilage degeneration by a conventional X-ray imaging (roentgen photograph) and MRI scan. The presence or absence of cartilage degeneration also can be checked by observing cartilage by use of an arthroscope (a kind of endoscope); however, in this method, a doctor in charge touches the site of the cartilage surface layer by use of a tool such as forceps under an arthroscope and determines the presence or absence of cartilage degeneration based on a sense of touch. Because of this, early detection is mostly left in the experience and skill of the doctor. In addition, there is a problem that the border line between normal cartilage and degenerative cartilage cannot be clearly identified.
If there is a non-Invasive or less-invasive examination method that enables early detection of cartilage degeneration without depending upon the experience and skill of a doctor alone, the presence or absence and the progress of cartilage degeneration can be figured out and therapeutic strategy can be easily created. As the non-invasive or less-invasive examination method, a method using an in-vivo imaging technique for visualizing a living tissue is known. As the in-vivo imaging technique, various techniques are known, including positron emission tomography (PET), nuclear magnetic resonance imaging (MRI), ultrasonography (US) and photoacoustic imaging (PAI). Other than these, a fluorescence imaging technique such as fluorescent molecule tomography (FMT) is known, in which a fluorescent substance is focused on a site of interest in a living body and the site is captured highly sensitively. The fluorescence imaging technique has attracted attention because it can non-invasively visualize a site of interest in a site specific manner.
In order to apply the aforementioned in-vivo fluorescence imaging technique to articular cartilage, several techniques relating to an imaging probe specifically binding to an articular cartilage tissue and accumulating there have been proposed. In Patent Literature 1, a cartilage marker specifically binding to cartilage matrix is described, which is obtained by allowing a signal generation means, such as a fluorescent substance, to bind to a polyarginine peptide having 6 to 20 arginine residues or a polylysine peptide having 6 to 20 lysine residues. Further in Patent Literature 2, a cartilage tissue marker is described, which consists of a lysine oligomer derivative obtained by allowing a group capable of generating or absorbing an electromagnetic wave to bind to a lysine oligomer in which ε-amino group of lysine and a carboxyl group are connected via a peptide bond.